The second study (abstract # 24-LB) evaluated the effects of treatment for two months with ZGN-201 on body weight and metabolic parameters in overweight canines. In animals fed a high fat, high fructose (HFF) diet, daily oral treatment with ZGN-201 promoted loss of 81 percent of excess body weight and reduced food intake by 29 percent. Glycerol and ketone body levels increased, reflecting enhanced lipolysis and fat oxidation. ZGN-201 treatment reversed 75 percent of the abnormality in the plasma glucose excursion during the oral glucose tolerance tests, despite a reduction in insulin secretion. Study author Alan Cherrington, Ph.D., professor of medicine and molecular physiology and biophysics at Vanderbilt University and former American Diabetes Association president, said, "These results suggest that, in addition to reducing body weight in obese animals, MetAP2 inhibitor treatment appears to overcome the defect in hepatic glucose uptake caused by a high fat, high fructose diet. These findings uncover a potentially important regulatory principle controlling blood glucose and highlight the potential for use of MetAP2 inhibitors in the treatment of type 2 diabetes."

"While our understanding of the biology of obesity continues to evolve, more and more research points to the role of adipose tissue itself as an important component of the disease," said Randy J. Seeley, Ph.D., professor of medicine and director of the Center of Excellence in Obesity and Diabetes at the University of Cincinnati College of Medicine, and a member of Zafgen's scientific advisory board. "Zafgen's approach using MetAP2 inhibitors aims to target the underlying differences between obese and lean individuals by impacting how the body metabolizes fat in those who are obese. ZGN-201 works by restoring control of adipose tissue lipolysis (breakdown of fat stored in fat cells), ketogenesis, food intake and fat synthesis, to release fat that is then used by the body as fuel - as opposed to being stored - driving weight loss."

SOURCE Zafgen, Inc.